NIR-II photo- and sono-responsive hyaluronic acid-capped nanozymes for glioblastoma-targeting theranostics

Glioblastoma is the most aggressive and heterogeneous astrocytic tumor, with its intracranial location limiting the efficacy of conventional therapies. This study presents the synthesis of a multifunctional nanocomplex utilizing borophene nanosheets (B NSs) as a substrate. Gold nanoparticles (Au NPs) are modified onto the surface of B NSs to create Schottky heterojunctions (BAu). This is followed by co-precipitation solvothermal synthesis incorporating silver sulfide (Ag₂S) and hyaluronic acid (HA) as a capping agent, yielding B-Au-Ag₂S-HA (BAA-HA). The Schottky heterojunction reduces the bandgap and accelerates charge carrier separation, significantly enhancing the sonodynamic therapy (SDT) efficiency of B NSs. In comparison to B NSs, BAA-HA exhibits significantly improved photothermal conversion efficiency under 1064 nm laser irradiation, facilitating the cascade catalysis of glucose oxidase-like (GOx-like) and catalase-like (CAT-like) enzymes. This accelerates glucose and H₂O₂ decomposition, increasing O₂ supply to amplify SDT efficacy and induce immunogenic cell death (ICD), inducing a robust anti-tumor immune response. Ultrasound-targeted microbubble destruction technology is employed to transiently open the blood-brain barrier, allowing for targeted delivery of BAA-HA to glioblastoma cells via HA-mediated recognition of the CD44 receptor. Additionally, the NIR-II fluorescence properties of Ag₂S enable precise tumor imaging, guiding multimodal synergistic therapy. This platform provides a promising strategy for treating deep-seated tumors, integrating therapeutic and diagnostic functions to enhance efficacy and precision.